This paper will describe the current planning for exploration-class missions, emphasizing the medical, and human factors aspects of such expeditions. The details of mission architecture are still under study, but a typical Mars design reference mission comprises a six-month transit from Earth to Mar, eighteen months in residence on Mars, and a six-month transit back to Earth. Physiological stressors will include environmental factors such as prolonged exposure to radiation, weightlessness in transit, and hypogravity and a toxic atmosphere while on Mars. Psychological stressors will include remoteness from Earth, confinement, and potential interpersonal conflicts, all complicated by circadian alterations. Medical risks including trauma must also be considered. Results of planning for assuring human health and performance will be presented.